Investigating The Effects Of Respiratory Gated Imrt Treatment Delivery On Survival

Purpose/Objective: Respiratory gating is increasingly being used to improve the conformality of radiation treatment delivery reducing the risk of normal tissue toxicity and enabling the delivery of higher doses of radiation than was previously possible in selected patients. The use of respiratory gating prolongs treatment delivery time by a factor of 2–3.3 and alters the pattern of radiation treatment by dividing one continuous fraction into multiple exposures of less than 0.2 Gy per exposure with each exposure separated by seconds. Previous publications examining very low doses of irradiation and separating exposures by milliseconds to seconds have suggested that these adjustments in delivery can alter the radiation sensitivity of cells both in vitro and through modeling. Furthermore, there is mounting evidence that prolonging treatment delivery time leads to decreased efficacy. The purpose of this study was to determine in vitro if the delivery of radiotherapy through respiratory gating, and/or IMRT, alters the biologic effectiveness of treatment when compared to continuous radiotherapy. Materials/Methods: An experimental schema was designed for irradiating cells in vitro to a total dose of 2 Gy using each method of radiation delivery either alone or in combination. A non-IMRT/non-gated radiotherapy arm with a slower dose rate but equivalent total treatment time was added to allow for direct comparison with two of the experimental arms while removing total treatment time as a confounding variable. Experiments were conducted on the V79 Chinese Hamster lung fibroblast cell line because of its high alpha/beta ratio and short repair half life. Experiments were conducted on four separate days on four wells of plated cells each day in each arm for a total of sixteen wells. Efficacy of each treatment method was assessed by clonogenic assay. Additionally, survival fraction results for each arm were estimated using the incomplete repair model as developed by Thames and later generalized to multiple fractions by Nilsson et al. Results: The experimental results are shown in table 1. Measured survival fractions for each arm were very similar to one another. Mean survival values were well within the range of one standard error of one another and no significant difference in cell kill for each of the treatment arms was detected. These findings were in agreement with the predicted results of the generalized incomplete repair model.Table 1 Conclusions: This in vitro experiment demonstrates that the use of respiratory gating does not change the radiobiologic effectiveness of radiotherapy when compared to continuous therapy. Furthermore, cell kill is not appreciably changed with the addition of IMRT to gated radiotherapy. Predictive modeling suggests that a significant change in effectiveness might be observed with larger doses per fraction and longer total irradiation times.